The immunomodulatory protein thymopoietin has been isolated from bovine and human thymus. Additionally, small peptides have been chemically synthesized which mimic the biological activity of thymopoietin. See, e.g. U.S. Pat. No. 4,505,853 and corresponding EP Application No. 146,266.
A large body of articles and patents have now been published relating to such proteins and synthesized peptides. U.S. Pat. No. 4,190,646 discloses the pentapeptide thymopentin which is the active site of thymopoietin and has the sequence Arg-Lys-Asp-Val-Tyr, as well as peptide compositions in which various groups are substituted onto the amino and/or carboxyl termini of this pentapeptide.
Two distinct thymopoietin receptors (TPR) on the human T cell lines CEM and MOLT-4, have been identified. The TPR of the CEM line has been termed .alpha. and that of the MOLT-4 line is called .beta. [G. Heavner et al, Regulatory Peptides, 27:257-262 (1990)]. Some relationship between .alpha. and .beta. TPR activation by thymopentin and its capacity to effect changes in the immune system, particularly their activity upon lymphocytes and monocytes, have been noted.
Further, thymopoietin is known to regulate cholinergic neuromuscular transmission. [G. Goldstein et al, Science, 204:1309-1310 (1979) and T. Audhya et al, Int. J. Peptide Protein Res., 22:568-572 (1983); M. Quik et al, J. Neurochem., 53(4):1320-1323 (1989)]. This neuromuscular effect is caused by thymopoietin binding to the nicotinic acetylcholine receptor, a ligand-regulated ion channel from the vertebrate neuromuscular junction and fish electric organ, F. Revah et al, Proc. Natl. Acad. Sci. USA. 84:3477-3481 (1987). This constitutes a third TPR. This activity has been termed .gamma., and molecules capable of affecting the nicotinic acetylcholine receptor are known as being .gamma. positive. Thymopoietin is present within the brain, as are .gamma. type TPR, so that thymopoietin is almost certainly involved in brain function. .gamma. positive molecules are associated with activity on nerve cells, including corticotropin releasing factor (CRF) function.
More recently, thymopentin has been identified as an antagonist of stress-induced changes, exhibiting stress-protective activity [V. Klusa et al, Regulatory Peptides, 27:35-365 (1990)].
There remains a need in the art for additional peptides as diagnostic and/or therapeutic agents which are useful in treating dysfunctions of the immune system in mammals, including those associated with aging and various physical conditions, as well as peptides useful for treating disorders in brain functions.